Fluorination Effects On Conformational Behaviors Of Benzylamine

Fluorination has become well-established strategies in the design of new drugs.It’s conducive to study the fluorination affects at the molecular level.Precise information on the conformational behaviors is not only essential for the structure-activity relationships,but also the key to understand the nature of the fluorination effect.This thesis will be focused on benzylamine and their fluorination derivatives by using high resolution pulse-jet Fourier transform microwave spectroscopic technique combining with quantum theoretical calculations.The conformational behaviors changing（including the molecular structures,conformational equilibria and internal dynamics）upon fluorinations will be discussed,from the molecular level,systematically to shed light on the nature of fluorination effects,which will be very helpful to tune,more rationally,the organic compounds.In the first chapter,the research of phenylalkylamine molecules was briefly introduced,then followed the fluorination effect and the theory of rotational spectroscopy.Finally,the work principle of microwave spectrometer and quantum theoretical calculation were listed.In the experimental part,to reveal the fluorination effect on the benzylamine,the rotationalspectraof4-fluorobenzylamine,3,4-difluorobenzylamine,2,4-difluorobenzymethylamine and 2,6-difluorobenzymethylamine were measured and assigned by pulsed jet Fourier transform microwave spectroscopy combined with quantum theoretical calculations.The rotational constants,¹⁴N nuclear quadrupole coupling constants and centrifugal distortion have been obtained.The complex geometry conformations in one molecule were caused by different orientations of lone pairs on amino.The conformers existed in the gas phase were measured and distinguished by rotational spectroscopy combined with quantum calculations,with analysing the corresponding hyperfine structures arisen from the nuclear quadrupole coupling effect.In addition,the transition line splittings caused by tunneling motion of the amino group has been observed in 2,4-difluorobenzylamine,the tunneling route and energy barrier has been determined by quantum chemical calculations.The last part is conclusion and prospective of the present study.The effects of numbers and positions of fluorine on the conformational behavior of benzylamine were discussed from molecular structures,conformational preferences and dynamics.All results show that the substitution of fluorine at different positions can bring great alterations to conformational preferences.When the ortho hydrogen is replaced by fluorine,the global minimum adopts such a structure that the aminao group tends to be perpendicular to the plane of the benzene ring and aminic hydrogen atoms points towards theπcloud.However,when fluorine replaces meta-or para-H,the most stable structure tends to be that the electron lone pair on nitrogen points towards the hydrogen atom in the ortho position forming a C-H···N weak hydrogen bond in the molecule.At the same time,the electron-withdrawing effect of the fluorine atom not only reduces the C-C bond length by 0.003～0.01（?）,but also increases the ring angle where it is located by 0.6°～2.9°.The further research would focus on the interaction of benzylamine and its complex,to have a better understanding of the interaction mechanisms between benzylamine and its receptor.